Ethyl Acetate → 4-Chloro-1-(2-cyclopropyl-1-methyl-1h-benzimidazol-6-yl)-2(1h)-pyridinone

To a suspension of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (75 g) in DMF (1.3 L) was added phosphorus oxychloride (29.8 ml) at room temperature, and the mixture was stirred at 45-50° C. under Ar atmosphere for 26 h. The mixture was poured into EtOAc (1.5 L), and washed with saturated NaHCO3 solution (1.5 L). The organic layer was separated, and aqueous layer was extracted with EtOAc (2.0 L) two times. The combined organic layer was washed with brine (1.0 L), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in EtOAc/THF (1/1, 700 ml), and NH silica gel (100 g) was added to the solution. The mixture was filtered through a plug of NH silica gel (500 g) with EtOAc as an eluent to give the title compound (47.0 g) as a pale yellow solid.

1. washwashed with saturated NaHCO3 solution (1.5 L)
2. customThe organic layer was separated
3. extractionaqueous layer was extracted with EtOAc (2.0 L) two times
4. washThe combined organic layer was washed with brine (1.0 L)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was dissolved in EtOAc/THF (1/1, 700 ml)
8. additionNH silica gel (100 g) was added to the solution
9. filtrationThe mixture was filtered through a plug of NH silica gel (500 g) with EtOAc as an eluent

ORDレコード

ord-ea4c6e18e73b4f119bcc4fc15b3a8b45

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09365540B2